Hemophilia – Gene Therapy .

uniQure has built an exciting portfolio of clinical and pre-clinical programs focused on hemophilia.

uniQure has built an exciting portfolio of clinical and pre-clinical programs focused on hemophilia. This overall effort is well supported by uniQure’s proprietary position with our AAV5 viral vector, which has shown particular affinity for reaching the liver. AAV5 has the benefit of a low prevalence of pre-existing anti-AAV5 antibodies in patients screened to date in uniQure’s clinical trials and as indicated in medical literature. uniQure also has gained extensive experience in the development and regulatory approval of the first gene therapy approved in the Western world: Glybera.

Hemophilia B

uniQure is developing a gene therapy for hemophilia B, a severe orphan blood clotting disorder. The program’s gene therapy product candidate consists of an AAV5 vector carrying a therapeutic human Factor IX, or FIX, gene cassette that uniQure has exclusively licensed from St. Jude Children’s Research Hospital in Memphis, Tennessee. uniQure is currently conducting a Phase I/II study of AMT-060 in patients with severe hemophilia B and advanced joint disease.

In December 2016, the Company presented updated clinical data from our Phase I/II trial (view press release). In January 2017, AMT-060 received Breakthrough Therapy designation from the U.S. Food and Drug Administration in January 2017 based on results from this ongoing, dose-ranging study (view press release).

The data from our Phase I/II study demonstrate AMT-060 is delivering sustained and significantly improved clinical benefits to patients suffering from severe hemophilia B by enabling them to discontinue bi-weekly infusions of FIX replacement therapy and to essentially eliminate the risk of spontaneous bleeding. We are observing a therapeutic benefit from AMT-060 that is clearly superior to their previous prophylactic FIX replacement therapy regimen, even in patients with advanced joint disease who still experienced many bleeds despite prophylaxis with FIX.

At both doses evaluated, AMT-060 appears to be safe and well-tolerated with no loss of FIX activity, no activation of T-cell response and no development of inhibitors for any of the 10 patients in the study.

The data from this ongoing study demonstrate clinically significant and sustained increases in FIX activity, substantial reductions in FIX replacement usage and a near cessation of spontaneous bleeding episodes.

AMT-060 has demonstrated a very low screening failure rate, with all patients screened in the study testing negative for pre-existing anti-AAV5 NABs, which suggests that a large proportion of the hemophilia patient population may be eligible for treatment with AMT-060. The proprietary elements of AMT-060, including our fully-humanized FIX gene cassette and AAV5 vector, are the only gene therapy components clinically demonstrated in hemophilia B to be safe, effective, and durable for up to six and a half years. These factors, along with our commercial-scale manufacturing capabilities, differentiate AMT-060 from other hemophilia gene therapies in development, and we look forward to advancing our program into a late-stage clinical study.

Hemophilia A

As another indication important to uniQure’s efforts in liver/metabolism, the Company is in pre-clinical evaluation for a gene therapy to treat hemophilia A. We expect to provide an update on this program sometime in the first half of 2017.